Prostaglandins (hereinafter, referred to as PG(s)) are members of class of organic carboxylic acids, which are contained in tissues or organs of human or other mammals, and exhibit a wide range of physiological activity. PGs found in nature (primary PGs) generally have a prostanoic acid skeleton as shown in the formula (A):
On the other hand, some of synthetic analogues of primary PGs have modified skeletons. The primary PGs are classified to PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PGJs according to the structure of the five-membered ring moiety, and further classified into the following three types by the number and position of the unsaturated bond at the carbon chain moiety:Subscript 1: 13,14-unsaturated-15-OHSubscript 2: 5,6- and 13,14-diunsaturated-15-OHSubscript 3: 5,6-, 13,14-, and 17,18-triunsaturated-15-OH.
Further, the PGFs are classified, according to the configuration of the hydroxyl group at the 9- and 11-position, into α type (the hydroxyl group is of an α-configuration) and β type (the hydroxyl group is of a β-configuration).
PGE1 and PGE2 and PGE3 are known to have vasodilation, hypotension, gastric secretion decreasing, intestinal tract movement enhancement, uterine contraction, diuretic, bronchodilation and anti ulcer activities. PGF1α, PGF2α and PGF3α have been known to have hypertension, vasoconstriction, intestinal tract movement enhancement, uterine contraction, lutein body atrophy and bronchoconstriction activities.
The present inventor has already found that prostaglandin compounds open chloride channels, especially ClC channels, more especially ClC-2 channel (US patent publication No. 2003-0130352, this cited reference is herein incorporated by reference). Further, the present inventor has already found that chloride channel openers have wide range of pharmacological activities (US patent publication Nos. 2003-0130352 and 2003-0166632, these cited references are herein incorporated by reference).
The chloride channel opener for the treatment of constipation was reported to have an adverse event such as nausea (Annual Meeting of the Digestive Disease Week. 372, 2003 (Abstract)).
However, it is not known how to relieve the adverse event such as nausea of the chloride channel openers.